This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Even 25 years after the HIV epidemic began, an effective AIDS vaccine is still unavailable. Multiple vaccine strategies (ie, viral-like particles i.v. or DNA-prime/vector boost i.m.) have been developed to generate immune responses, but none have protected from eventual disease progression. The live-attenuated SIV ([unreadable]nef) in non-human primate models has been shown to induce a strong specific immune response against SIV proteins and to protect animals from subsequent SIV challenge;however, viral replication and pathogenicity has been associated with SIV [unreadable]nef. The focus of this project is to amend AIDS vaccine strategies with gene transfer technologies such as using replication defective lentiviral vectors, co-expressing immuno-modulatory cytokine genes, transducing target cells ex vivo. We are developing a new series of SIV-based lentiviral vectors to efficiently transduce CD34+ hematopoietic stem/progenitor cells ex vivo, expand the transduced cells in culture, induce their differentiation to professional antigen presenting cells (like macrophages or dendritic cells), for expression of viral antigens and the cytokine Flt3L. These transduced cells will be used for vaccination of the autologous host. Vaccinated rhesus will be evaluated for immunological parameters and for protection from challenged with SIVmac.